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Biomedical subjects

T J Ervin

Publications and source records attributed to T J Ervin.

At least 37 records · Page 2Linked to original sources
PubMed1986

Pathology of surgery after induction chemotherapy: an analysis of resectability and locoregional control.

At the Dana-Farber Cancer Institute Head and Neck Cancer Clinic, 114 previously untreated patients with advanced squamous cell carcinoma of the head and neck (17% stage III; 83% stage IV) were managed with induction chemotherapy using cis-platinum, bleomycin, and methotrexate, followed by definitive extirpative surgery and/or radiation therapy. The present report evaluates this group from a surgical and surgical pathology standpoint. The following aspects are evaluated: predictability of, and conversion to, resectability during induction chemotherapy; ease of surgical technique and intraoperative assessment; patterns of pre-op and post-op risks and complications; gross and histopathologic observations of the extent and character of residual primary and nodal disease, particularly after a response to chemotherapy; patterns of locoregional control or failure related to treatment variables. The issues subsequently addressed include: how does chemotherapy affect the operative candidacy and resectability of proposed surgical patients? Could, or should surgery be eliminated in the management of some patients treated with induction chemotherapy? Can less radical surgery be contemplated in patients significantly "downstaged" by prior chemotherapy treatment? Is increased locoregional or distant metastatic control observed in these patients? What is the role of surgery in the responder to chemotherapy?

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1986

Phase I study of continuous-infusion cisplatin.

Cisplatin was administered to 21 patients as a continuous infusion over 5 days. Doses of 20, 25, and 30 mg/m2/day were studied. When administered in 3 L of normal saline/day, continuous-infusion cisplatin at a dose of 30 mg/m2/day was associated with neuropathy in two of nine patients and creatinine elevations (greater than 2 mg/dl) in four. No neurotoxicity or nephrotoxicity was observed at lower doses. Severe thrombocytopenia (less than 50,000/microliter) was unrelated to dose and occurred in 19% of the courses. Leukopenia was minimal. Nausea and vomiting were easily controlled. No toxicity was seen in 38% of the courses. Nineteen patients were evaluable for response. Six patients achieved partial response (32%), five had minimal response (25%), and eight had progressive disease (42%) in this group. Seven patients had received cisplatin previously as a bolus treatment (20 mg/m2/day for 5 days) and failed on chemotherapy. Among these patients there was one with partial response, three with minimal response, and three with progressive disease. It is concluded that continuous-infusion cisplatin, as given in this protocol, is well-tolerated at a dose of 25 mg/m2/day and can result in responses in patients failing bolus cisplatin at high doses.

Adult↗
PubMed1985

Combined modality treatment of head and neck cancer with cisplatin, bleomycin, methotrexate-leucovorin chemotherapy.

The multidisciplinary treatment results of 114 patients with advanced, untreated Stage III and IV squamous cell carcinoma of the head and neck region are reported. Induction chemotherapy with two cycles of cisplatin 20 mg/m2/day intravenous bolus days 1 through 5, bleomycin 10 mg/m2/day as a continuous infusion days 3 through 7, and methotrexate 200 mg/m2 intravenous bolus on days 15 and 22 with leucovorin rescue was utilized before definitive surgery and/or radiation therapy. The total response rate was 78% with 30 (26%) patients achieving complete response and 59 (52%) patients achieving partial response. Patient age, performance status, histologic grade of tumor, and tumor site did not predict response to chemotherapy. Induction chemotherapy was well tolerated with myelosuppression and nephrotoxicity being dose-limiting in a few patients. The toxicity of subsequent local treatment with surgery and/or radiation is reported with an analysis of local treatment failures. A strong correlation was noted between local control of tumor and postchemotherapy tumor size before local treatment.

Adult↗
PubMed1985

Treatment of the blastic transformation of chronic granulocytic leukemia using high dose BCNU chemotherapy and cryopreserved autologous peripheral blood stem cells.

Seven nonsplenectomized patients with blastic CGL have received high dose BCNU chemotherapy followed by cryopreserved peripheral blood stem cells (PBSC). The PBSC obtained at diagnosis were stored in the vapor phase of liquid nitrogen in 10% dimethyl sulfoxide for 11-46 months prior to use. Patients received 2.9 X 10(8) (1.9-7.8) thawed washed mononuclear cells/kg over 30 minutes with minimal morbidity. One patient was not rendered pancytopenic and died with blastic leukemia at 4 months. One patient, previously treated with daily busulfan, died of progressive hepatic failure 2 months after high dose BCNU. Restoration of the chronic phase of CGL was observed in the remaining five patients. Peripheral blood counts returned to normal ranges after a median of 19 days. Median survival for all patients is 11 months. Cytogenetic studies revealed elimination of acquired aneuploid cell lines in four of seven patients with persistence of Ph1. We conclude that: 1) frozen PBSC retain their viability for up to 4 years after cryopreservation and 2) the use of autologous PBSC following ablative chemotherapy may be associated with both symptomatic and karyotypic improvement in patients with blastic CGL.

Adolescent↗
PubMed1985

Treatment of perineural metastasis from squamous carcinoma of the skin with aggressive combination chemotherapy and irradiation.

Perineural metastasis from squamous cell carcinoma is quite rare. The treatment of such metastasis in the head and neck region is difficult due to base of skull or intracranial involvement by tumor. Surgery and radiotherapy may provide local control, but patients often fail distantly. We present a patient with squamous cell carcinoma presenting with perineural metastasis who was successfully treated with combination chemotherapy and definitive radiation therapy. Suggestions of therapeutic management are made of this uncommon clinical problem.

Aged↗
PubMed1985

Treatment complications after sequential combination chemotherapy and radiotherapy with or without surgery in previously untreated squamous cell carcinoma of the head and neck.

One hundred consecutive patients with previously untreated advanced squamous cell carcinoma of the head and neck were treated with induction combination chemotherapy followed by definitive surgery and/or radiotherapy, and were evaluated for radiotherapy related toxicity. The induction regimen consisted of cisplatin, bleomycin and methotrexate/leucovorin. Acute toxicity consisted predominantly of mucositis and weight loss, and was mild or moderate by degree in 94% of patients. Six percent of patients experienced severe or life threatening acute toxicities. Two acute toxic deaths were noted in this series, one from a combination of mucositis, weight loss and infection and one from hypoglycemia of unknown origin. Thirty-five percent of patients had radiation treatment interrupted briefly because of acute toxicity. Toxicity was greatest in patients who were nonresponders to induction chemotherapy and such may have been related to the continued presence of advanced tumor. Radiotherapy dose, surgical intervention and age did not have an impact on the presence or degree of acute toxicity. Late toxicities included: hypothyroidism in 32% of patients tested: osteoradionecrosis in 5% of patients, associated primarily with a composite resection (4 of 5 cases); and soft tissue ulcerations in 3%. Taken together, these data indicate that induction combination chemotherapy did not significantly increase the toxicity of subsequent radiotherapy with or without surgery.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1985

Alkylating agent resistance: in vitro studies with human cell lines.

Development of in vitro resistance to HN2 (also called mustargen or mechlorethamine hydrochloride), N,N'-bis(2-chloroethyl)-N-nitrosourea (BCNU), and cisplatin [cis-diamminedichloroplatinum(II)] was achieved in two human cell lines, the Raji/Burkitt lymphoma and a squamous cell carcinoma of the tongue. A 10- to 20-fold increase in resistance relative to the parental line was achieved in 3-4 months of continuous selection pressure. At this time, further increase in selection pressure resulted in cell death, while removal of drug led to rapid loss of resistance. However, by holding selection pressure constant over 8-12 months, semistable clones ranging in resistance up to 8- to 12-fold were obtained. The half-life for resistance loss upon removal of drug was 2-3 months. In the presence of intermittent low concentrations of the alkylating agent, resistance has been maintained in excess of 9 months. With one exception, the growth kinetics of the resistant clones were slightly slower than those of the parental lines. Cross-resistance studies were performed against HN2, BCNU, cisplatin, phenylalanine mustard, and hydroperoxycyclophosphamide. There was, in general, a lack of cross-resistance. We conclude that stable resistance to alkylating agents is produced with difficulty. We propose that these semistable cloned human tumor lines represent clinically relevant models for the study of alkylating agent resistance and that the cross-resistance patterns among these cells have important therapeutic and mechanistic implications.

Alkylating Agents↗
PubMed1985

Primary lymphomas of the central nervous system: patterns of failure and factors that influence survival.

Primary lymphomas of the CNS are rare tumors accounting for less than 2% of all extranodal non-Hodgkin's lymphomas. The treatment for this disease has been disappointing. Radiation therapy and surgery have produced consistently poor control of this disease, with a median survival of 15 months. We have reviewed ten cases of primary lymphoma of the CNS treated at the Joint Center for Radiation Therapy or Dana-Farber Cancer Institute (Boston) from 1968 to 1981. All patients had biopsy-proven CNS lymphomas without systemic disease at presentation. In our series, control of CNS lymphoma was seen only in patients receiving craniospinal radiation or CNS-penetrating chemotherapy.

Adolescent↗
PubMed1985

Phenotypic heterogeneity in cultured human head and neck squamous cell carcinoma lines with low-level methotrexate resistance.

Low-level methotrexate (MTX) resistance (less than 20-fold) was induced by gradual selection pressure in four human head and neck squamous cell carcinoma lines established in culture from biopsies of patients not previously treated with MTX. Each parental and resistant line was characterized with respect to MTX uptake and polyglutamylation, dihydrofolate reductase (DHFR) content, and growth rate. Relative DHFR gene copy numbers and amounts of DHFR-related cytoplasmic messenger RNA were analyzed by plasmid complementary DNA hybridization in a dot blot assay and were correlated with the amount of gene product. The resistant lines were not cloned in order to simulate in vitro the conditions which might exist in an in vivo setting, where multiple resistant subpopulations of cells may be present in a tumor. The study was restricted to cells with low-level resistance since these are likely to be the clinically most relevant type. Of the four resistant lines characterized, one showed a severe defect in MTX uptake and polyglutamylation, another was a DHFR overproducer with only small changes in uptake and polyglutamylation, a third was likewise a DHFR overproducer but also showed lower MTX uptake, and the fourth was minimally altered except for growth rate. The diversity in resistance phenotype among these cells in vitro suggests that in vivo resistance in patients with head and neck carcinoma who are treated with MTX may similarly involve multiple mechanisms and that further therapeutic intervention using MTX or other antifolates should take this into account.

Biological Transport↗
PubMed1985

Multidisciplinary treatment of advanced squamous carcinoma of the head and neck.

Advanced squamous carcinoma of the upper aerodigestive tract continues to be a therapeutic challenge. With recent advances in chemotherapy, systemic treatment has been used in an attempt to improve treatment results produced by radiation therapy and/or surgery. Such multidisciplinary experimental approaches have given new hope for cure in stage III and stage IV disease, but have reopened old questions as to the natural history and underlying biology of this disease. Multidisciplinary treatment, whether synchronous or sequential, appears to improve survival for stage III and stage IV patients achieving a complete response to chemotherapy plus irradiation. The role of surgery or radiotherapy for control of primary or nodal disease remains unchanged and is an essential component of all curative treatment plans.

Carcinoma, Squamous Cell↗
PubMed1984

Advanced squamous carcinoma of the head and neck. A preliminary report of neoadjuvant chemotherapy with cisplatin, bleomycin, and methotrexate.

Between Oct 1, 1979 and Aug 1, 1982, 93 patients with advanced squamous carcinoma of the head and neck were given neoadjuvant treatment with cisplatin, bleomycin sulfate, and methotrexate before standard local treatment. Ninety-three patients were evaluable for response. The response rates were as follows: complete response, 24%; partial response, 64%; and no response, 12%. Differences in primary tumor site, performance status at presentation, histologic grade, and tumor size did not correlate with response to this chemotherapy. For patients achieving notable tumor reduction to 2 cm or less, standard local treatment with either surgery plus radiotherapy or high-dose radiotherapy alone was effective in controlling local disease. For patients with larger tumor masses following neoadjuvant chemotherapy, surgical resectability appeared to improve local control rates. In our series, patients not receiving maximal standard local treatment often had relapse of local disease despite favorable responses to chemotherapy.

Adolescent↗
PubMed1984

The role of post-operative radiation therapy in the treatment of malignant tumors of the parotid gland.

Twenty-nine patients treated with postoperative radiotherapy for malignant tumors of the parotid gland were reviewed at the Joint Center for Radiation Therapy. Most patients were treated between 5,000 and 6,500 rad. All were treated because of microscopic residual disease, extra capsular extension, or tumor close to the facial nerve. The overall results showed one in-field failure, two marginal recurrences, and eight patients failed distantly. Poor prognostic factors included high-grade, extracapsular extension, and nodal involvement. We conclude that patients with malignant tumors of the parotid should be treated with postoperative radiation therapy if any of the bad prognostic signs are present. This may enable the surgeon to spare the facial nerve and obtain local control results equal to or better than more radical surgical procedures.

Adolescent↗
PubMed1984

Cellular X-ray repair parameters of early passage squamous cell carcinoma lines derived from patients with known responses to radiotherapy.

We have investigated X-ray survival parameters and repair of potentially lethal damage ( PLDR ) in ten early passage squamous cell carcinoma cell lines derived from patients who were biopsied before initiation of radiotherapy or after radiation therapy failure. Radiosensitivity (D0) ranged from 1.07 to 1.93 (Gy), extrapolation numbers (-n) from 1.17 to 2.14 and PLD recovery at 24 h from 1.4 to 20.3. Despite significant differences in these parameters amongst the cell lines, a firm correlation between radiocurability and any individual radiobiological parameter could not be established. Our data suggest that the mechanisms associated with radioresistance are complex and that any single radiobiological parameter may not predict clinical success or failure.

Carcinoma, Squamous Cell↗
PubMed1984

Development of methotrexate resistance in a human squamous cell carcinoma of the head and neck in culture.

Four methotrexate (MTX)-resistant sublines of a human squamous cell carcinoma (SCC15) were established in culture by progressive dose escalation. The biochemical basis of resistance was studied. The line with the lowest resistance (R1) had a normal dihydrofolate reductase (DHFR) content but showed decreased MTX transport and polyglutamation. Lines of intermediate resistance (R2 and R3) showed an increased DHFR content and DHFR gene copy number and a defect in MTX transport. The line with the greatest resistance (R4) showed increased DHFR content and gene copy number but nearly normal MTX transport. These results demonstrate that multiple mechanisms of MTX resistance occur in human epithelial cells in culture. We also find evidence of alterations in DHFR gene expression. The MTX-resistant cells were either not cross-resistant or only partly cross-resistant to two lipophilic MTX ester derivatives. These compounds are of potential therapeutic interest for the treatment of MTX-resistant tumors.

Biological Transport↗
PubMed1984

Preparation of human hyperimmune globulin to Haemophilus influenzae b, Streptococcus pneumoniae, and Neisseria meningitidis.

As a first step in exploring the feasibility of passive antibody prophylaxis and therapy of serious infections caused by common encapsulated bacteria, we have immunized healthy adults with Haemophilus influenzae type b vaccine, 14-valent pneumococcal vaccine, and meningococcal group A and C vaccine; collected plasma by repeated pheresis; and purified a hyperimmune globulin termed bacterial polysaccharide immune globulin by the cold-ethanol fractionation method of Cohn and Oncley. Specific antibacterial antibody concentrations were measured in individual donors before and after immunization. In addition, antibody concentrations were measured in plasma pools prepared from immunized donors and from unimmunized controls and in the immunoglobulin-containing Cohn-Oncley fractions II and III derived from the respective plasma pools. A comparison of Cohn-Oncley fractions II, which contain primarily immunoglobulin G and which are used therapeutically as immune globulin, revealed that antibody to H. influenzae type b was enriched 15.3-fold and that antibody to meningococcal serogroups and pneumococcal types was enriched a mean of 4.4-fold (range, 1.2- to 9.9-fold). Enrichment of antibacterial antibody in Cohn fraction III, which contains substantial amounts of immunoglobulin M and immunoglobulin A in addition to immunoglobulin G, closely paralleled that in fraction II. Only antibodies to pneumococcal types 1 and 7 were increased disproportionately in fraction III. Based on the clinical experience that conventional immune serum globulin at a dose of 100 mg/kg protects agammaglobulinemic patients for ca. 1 month, we estimate that bacterial polysaccharide immune globulin, in similar dosage, will provide protection from systemic H. influenzae type b infection for 4 to 6 months and from pneumococcal and meningococcal infections for 3 to 4 months.

Antibodies, Bacterial↗
PubMed1984

Incidence of hypothyroidism following multimodality treatment for advanced squamous cell cancer of the head and neck.

The incidence of chemical hypothyroidism, as manifested by elevated thyroid stimulating hormone (TSH) levels, has been estimated to be as high as 25% after radiation therapy and 45% after radiation therapy and surgery to the neck for treatment of nodal metastases from squamous carcinoma of the head and neck. We prospectively evaluated 43 previously untreated patients seen in the Dana Farber Cancer Institute Interdisciplinary Head and Neck Service who were treated with aggressive combination chemotherapy in addition to standard surgery and/or radiotherapy. All patients were serially monitored for serum TSH, serum T4, and clinical evidence of hypothyroidism. Following cis-platinum, bleomycin, and methotrexate chemotherapy and subsequent surgery and/or radiotherapy, decreased thyroid reserve appeared in 37% of patients at a median follow-up of 9 months. Thirty percent of patients receiving radiotherapy alone and 43% of patients receiving surgery and radiotherapy developed elevated TSH levels. Only one patient developed clinical symptoms. Other patients were asymptomatic despite persistently elevated TSH levels. Abnormalities appeared within the first 4 months after completion of all therapy and were slowly progressive. The addition of combination chemotherapy does not appear to increase the incidence or severity of thyroid dysfunction following radiation therapy and surgery to the neck. In view of the extended survival seen in patients treated with interdisciplinary regimens, we recommend that all patients receiving irradiation to the neck--particularly those patients having neck dissections or total laryngectomies--have routine thyroid function studies performed following the cessation of treatment.

Adolescent↗
PubMed1983

Radiobiologic research for head and neck cancer therapy. Therapeutic implications.

Hypoxic cell sensitizers, particle therapy, hyperthermia, and combinations of chemotherapy and radiotherapy have potential to increase the therapeutic ratio in future clinical radiotherapy treatment regimens. The biologic bases of these investigations are beginning to appear as avenues of clinical investigation.

Head and Neck Neoplasms↗